3,5-di[(tert-butyldimethylsilyl)oxy]-1-ethynylcyclohex-1-ene | 144699-08-1

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: 3,5-di[(tert-butyldimethylsilyl)oxy]-1-ethynylcyclohex-1-ene
• 英文别名: (TBSO)2C6H7CCH；tert-butyl-[(1S,5R)-5-[tert-butyl(dimethyl)silyl]oxy-3-ethynylcyclohex-2-en-1-yl]oxy-dimethylsilane
• CAS: 144699-08-1
• 化学式: C₂₀H₃₈O₂Si₂
• 分子量: 366.692
• InChiKey: IMPUKNVTXGBGNG-QZTJIDSGSA-N

物化性质

• 沸点：
  358.9±42.0 °C(Predicted)
• 密度：
  0.91±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.12
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,5-di[(tert-butyldimethylsilyl)oxy]-1-ethynylcyclohex-1-ene 在 盐酸 、 甲醇 作用下， 反应 3.0h， 生成 (3S,5R)-1-ethynyl-3,5-dihydroxycyclohex-1-ene
  参考文献：
  名称：

  Novel chiral precursors of 6-s-cis locked 1α,25-dihydroxyvitamin D3 analogues through selective enzymatic acylation

  摘要：

  The syntheses of selectively modified chiral A-ring precursors for the preparation of 17,25-dihydroxyvitamin D-3 analogues by regioselective enzymatic acylation are described. Candida antarctica lipase B (CAL-B) catalyzes the acylation of 1alpha,25-dihydroxy-19-nor-previtamin D-3 trans A-ring precursors 4 and 5 with high selectivity. The opposing regioselectivities observed for each pair of enantiomers is noteworthy: whereas CAL-B acylates the C-3 hydroxyl groups for derivatives of (3S,5R)-configuration, it catalyzes acylation at the C-5 hydroxyl group for substrates which possess (3R,5S)-stereochemistry. In relation to stereoisomer 4b, Chromobacterium viscosum lipase (CVL) showed opposite behavior to CAL-B, catalyzing acylation at the C-5 hydroxyl group with acceptable selectivity. In the enzymatic acylation of cis A-ring synthons 6 and 7, CVL gave total selectivity for acylation of the C-5 hydroxyl group of (3S,5S)-6 and the C-3 hydroxyl group of (3R,5R)-7. CAL-B also exhibits high selectivity towards the acylation of the C-3 hydroxyl in 19-nor-A-ring precursors with (3R,5R)-configuration. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(02)00149-0
• 作为产物：
  描述：

  莽草酸 在 吡啶 、 盐酸 、 4-二甲氨基吡啶 、 manganese(IV) oxide 、 正丁基锂 、 偶氮二异丁腈 、 三正丁基氢锡 、 二异丁基氢化铝 、 三乙胺 、 三苯基膦 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 101.0h， 生成 3,5-di[(tert-butyldimethylsilyl)oxy]-1-ethynylcyclohex-1-ene
  参考文献：
  名称：

  Synthesis of 1α,25-dihydroxy-19-norprevitamin D3

  摘要：

  We describe a convergent synthesis of 1-alpha,25-dihydroxy-19-norprevitamin D3 (3), an analogue of the hormone 1-alpha,25-dihydroxyvitamin D3 (1c) that is locked into the previtamin form.

  DOI：

  10.1016/s0040-4039(00)79117-9

文献信息

• Synthesis of 1α,25-Dihydroxyvitamin D Analogues Featuring a S2-symmetric CD-ring Core
  作者：Garrett Minne、Lieve Verlinden、Annemieke Verstuyf、Pierre De Clercq

  DOI：10.3390/molecules14020894

  日期：——

  Three analogues of 1a,25-dihydroxyvitamin D3 (calcitriol), featuring a trans-fused decalin C,D-core with local S2-symmetry, and possessing identical side-chain and seco-B,A-ring structures, have been synthesized starting from readily available (4aR,8aS)-octahydronaphthalene-1,5-dione (7). The very short sequences involve the simultaneous introduction of the side-chain and seco-B,A-ring fragments via Suzuki and Sonogashira coupling reactions. The analogues are devoid of relevant biological activity.

  我们从容易获得的 (4aR,8aS)-八氢萘-1,5-二酮 (7) 开始，合成了 1a,25-二羟维生素 D3（降钙素三醇）的三种类似物，它们具有局部 S2 对称的反式融合癸醛 C、D 核，以及相同的侧链和仲 B、A 环结构。这些极短的序列涉及通过铃木和 Sonogashira 偶联反应同时引入侧链和仲B,A 环片段。这些类似物没有相关的生物活性。
• Synthesis, biological activity, and conformational analysis of CD-ring modified trans-decalin 1α,25-dihydroxyvitamin D analogsElectronic supplementary information (ESI) available: Further experimental details. See http://www.rsc.org/suppdata/ob/b2/b209147j/
  作者：Yong-Jun Chen、Ling-Jie Gao、Ibrahim Murad、Annemieke Verstuyf、Lieve Verlinden、Christel Verboven、Roger Bouillon、Davide Viterbo、Marco Milanesio、Dirk Van Haver、Maurits Vandewalle、Pierre J. De Clercq

  DOI：10.1039/b209147j

  日期：2003.1.13

  series of analogs of 1,25-dihydroxyvitamin D3, the hormonally active metabolite of vitamin D3, characterised by the presence of a trans-fused decalin CD-ring system, possesses surprising biological activities in combination with specific structural modifications in the flexible parts of the molecule, when compared with the natural hydrindane derivatives. (1) A large difference in biological activity is observed

  1,25-二羟基维生素D3（维生素D3的激素活性代谢物）的新型类似物系列，其特征在于存在转融合的十氢化萘CD-环系统，具有令人惊讶的生物学活性，并且在柔性部位具有特定的结构修饰与天然的氢化茚衍生物相比时 （1）在20个异构体的反式十氢化萘类似物之间观察到生物学活性差异很大，其规律与通常观察到的天然环大小相反。（2）在seco-B环区域修饰的几种反式十氢化萘类似物，包括维生素原衍生物，具有明显的维生素D样活性，而相应的氢化茚衍生物则没有活性。这种行为的分子起源仍在研究中。
• Novel 9-Alkyl- and 9-Alkylidene-Substituted 1α,25-Dihydroxyvitamin D₃ Analogues: Synthesis and Biological Examinations
  作者：Urszula Kulesza、Lori A. Plum、Hector F. DeLuca、Antonio Mouriño、Rafal R. Sicinski

  DOI：10.1021/acs.jmedchem.5b00795

  日期：2015.8.13

  Continuing the structure–activity relationship studies in the vitamin D area, we designed and synthesized novel C-9 substituted calcitriol analogues, possessing different nonpolar groups at this position. 9α-Methyl-1α,25-(OH)2D3, both epimers of 9-methylene-10,19-dihydro-1α,25-(OH)2D3 as well as the parent vitamin with the “reversed” triene system, 9-methylene-19-nor-1α,25-(OH)2D3, were obtained from

  继续进行维生素D区域的结构-活性关系研究，我们设计和合成了新颖的C-9取代的骨化三醇类似物，在该位置具有不同的非极性基团。9α甲基1α，25-（OH）2 d 3，9-亚甲基10,19二氢-1α的两个差向异构体，25-（OH）2 d 3以及用“颠倒”三烯母体维生素系统，9-亚甲基-19-nor-1α，25-（OH）2 D 3，是从前维生素D的前体获得的，前体D是由Suzuki-Miyaura，Sonogashira或相应的A和C，D环片段的Stille偶联物构建的。导致后者的维生素及其与9-亚乙基的同系物的另一种合成途径涉及形成二烯作为相应的19-去甲维他命D化合物的前体。用威尔金森催化剂均相加氢制备9β-甲基-19-nor-1α，25-（OH）2 D 3，发现该类似物在体外最活跃。此外，9α-甲基-1α，25-（OH）2 D 3和9-亚甲基-19-nor-1α，25-（OH）2 D 3 尽
• Synthesis of two 6-s-cis locked stereoisomeric analogues of the steroid hormone 1α,25-dihydroxyvitamin D3: 1α,25-dihydroxy-19-nor-previtamin D3 and 1β,25-dihydroxy-19-nor-previtamin D3
  作者：Mónica Dı́az、Miguel Ferrero、Susana Fernández、Vicente Gotor

  DOI：10.1016/s0040-4039(99)02152-8

  日期：2000.1

  An efficient synthesis of A-ring precursors 8 and 9 from inexpensive commercially available (−)-quinic acid has been developed. A-Ring synthon 8 has been obtained through a short sequence (eight steps) in high overall yield (30%). One key step in the synthesis of A-ring precursor 9 is the selective deprotection of a silyl ether in an α,β-unsaturated ester 12. However, of note is the excellent yield

  已经开发了由廉价的可商购获得的（-）-奎尼酸有效合成A-环前体8和9的方法。通过短序列（八步）以高总产率（30％）获得了A-环合成子8。合成A环前体9的一个关键步骤是在α，β-不饱和酯12中对甲硅烷基醚进行选择性脱保护。但是，值得注意的是，Mitsunobu方法在衍生物15上的收率很高，这与构型的全部转化有关，生成了酯16。A环合成子8和9与适当的CD环/侧链片段的偶联7，提供了访问6-小号-顺式锁定类固醇激素1α的类似物，25-（OH）2 -D 3：1α，25-（OH）2 -19-也不-pre-d 3（3）的和新颖的1β，25-（OH）2 -19-或-pre-D 3（4）。
• Development of 14-<i>epi</i>-19-Nortachysterol and Its Unprecedented Binding Configuration for the Human Vitamin D Receptor
  作者：Daisuke Sawada、Yuya Tsukuda、Hiroshi Saito、Shinji Kakuda、Midori Takimoto-Kamimura、Eiji Ochiai、Kazuya Takenouchi、Atsushi Kittaka

  DOI：10.1021/ja201481j

  日期：2011.5.11

  In the study of the synthesis of 14-epi-19-norprevitamin D-3, we found 14-epi-19-nortachysterol derivatives through C6,7-cis/trans isomerization. We also succeeded in their chemical synthesis and revealed their marked stability and potent VDR binding affinity. To the best of our knowledge, this is the first isolation of stable tachysterol analogues. Surprisingly, 14-epi-19-nortachysterol derivatives exhibited an unprecedented binding configurations for the ligand binding pocket in hVDR, C5,6-s-trans and C7,8-s-trans triene configurations, which were opposite the natural C7,8-ene-configuration of 1 alpha,25(OH)(2)D-3.